N1-(4-chloro-3-fluorophenyl)-N2-(2-(2,6-dimethylmorpholino)ethyl)oxalamide | 1226788-76-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N1-(4-chloro-3-fluorophenyl)-N2-(2-(2,6-dimethylmorpholino)ethyl)oxalamide
• 英文别名: N'-(4-chloro-3-fluorophenyl)-N-[2-(2,6-dimethylmorpholin-4-yl)ethyl]oxamide
• CAS: 1226788-76-6
• 化学式: C₁₆H₂₁ClFN₃O₃
• 分子量: 357.812
• InChiKey: OWSZFCPQQWAEIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 2-(4-chloro-3-fluorophenylamino)-2-oxoacetate 、 4-(2-氨基乙基)-顺式-2,6-二甲基吗啉 以 乙醇 为溶剂， 以79%的产率得到N1-(4-chloro-3-fluorophenyl)-N2-(2-(2,6-dimethylmorpholino)ethyl)oxalamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening

  摘要：

  The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.049

文献信息

• SMALL MOLECULE CD4 MIMETICS AND USES THEREOF
  申请人：Sodroski Joseph

  公开号：US20120122834A1

  公开（公告）日：2012-05-17

  The invention provides for compounds of formula I: wherein Z is absent or (CR A R B ) n W; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHL, NR c R c , SH, S(O) m R c ; or (iii) R A and R B together form C(O); W is absent, C(O), C(O)O, C(O)NR c R c , O, S(O) m , or NR c R c ; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NR X R Y ; wherein R x and R y are each independently H, alkyl or aryl; X 1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each R c is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof.

  本发明提供了公式I的化合物：其中Z不存在或为（CRARB）nW;每个RA和RB都是独立的（i）H，烷基，烯基，炔基，环烷基，杂环烷基，芳基，杂芳基，芳基烷基，杂芳基烷基，卤代烷基，每个都可以选择性地取代;（ii）OH，ORc，NH2，NHL，NRcRc，SH，S（O）mRc;或（iii）RA和RB共同形成C（O）;W不存在，C（O），C（O）O，C（O）NRcRc，O，S（O）m或NRcRc;Y是可选取代的杂环，可选取代的杂芳基，可选取代的环烷基，可选取代的芳基或NRXRY;其中Rx和Ry各自独立地为H，烷基或芳基;X1选自卤素，甲基和羟基的群;X2是卤素;每个Rc都是独立的烷基，环烷基，杂环烷基，芳基，杂芳基，芳基烷基或杂芳基烷基，每个都可以选择性地取代;m为O，1或2;n为1,2,3,4,5或6;以及其药学上可接受的盐。
• US9776963B2
  申请人：——

  公开号：US9776963B2

  公开（公告）日：2017-10-03
• [EN] SMALL MOLECULE CD4 MIMETICS AND USES THEREOF<br/>[FR] MIMÉTIQUES CD4 À PETITE MOLÉCULE ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2010053583A2

  公开（公告）日：2010-05-14

  The invention provides for compounds of formula I: wherein Z is absent or (CRARB)nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHRc, NRcRc, SH, S(O)mRc; or (iii) RA and RB together form C(O); W is absent, C(O), C(O)O, C(O)NRcRc, O, S(O)m, or NRcRc; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NRXRY; wherein Rx and Ry are each independenly H, alkyl or aryl; X1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each Rc is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof.
• Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening
  作者：Judith M. LaLonde、Mark A. Elban、Joel R. Courter、Akihiro Sugawara、Takahiro Soeta、Navid Madani、Amy M. Princiotto、Young Do Kwon、Peter D. Kwong、Arne Schön、Ernesto Freire、Joseph Sodroski、Amos B. Smith

  DOI：10.1016/j.bmc.2010.11.049

  日期：2011.1

  The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. (C) 2010 Elsevier Ltd. All rights reserved.